BCL11A

BCL11 transcription factor A

2 disorders 2 untyped 2p16.1 gene with protein product

HGNC:13221 Monarch NCBI Gene 53335 ENSG00000119866 UniProt Q9H165 OMIM 606557

Previous symbols: EVI9. Aliases: BCL11A-XL, BCL11A-L, BCL11A-S, CTIP1, HBFQTL5, ZNF856, SMARCM1.

Normal function · from ai-gene-review (Q9H165, commit 79fe13b38970) · AI-generated, not KB evidence

BCL11A is a zinc-finger transcriptional regulator expressed in hematopoietic and neural tissues. Its longer isoforms act in the nucleus, associate with chromatin and nuclear bodies, and interact with transcriptional cofactors, including BAF chromatin-remodeling complexes. In adult erythroid cells, the XL isoform directly binds gamma-globin promoters through its C-terminal zinc-finger array and represses fetal-globin expression. BCL11A also regulates lymphoid and neuronal gene programs, with activating or repressive effects depending on the cellular context. Alternative splicing changes its zinc-finger complement and subcellular distribution, with localization varying by isoform and cellular context. Heterozygous loss of function causes a neurodevelopmental disorder that can include persistent fetal hemoglobin.

Directly represses RNA polymerase II transcription through sequence-specific regulatory DNA binding and cofactor engagement. The best resolved example is BCL11A-XL repression of gamma-globin in adult erythroid cells: its C-terminal zinc-finger array recognizes a distal promoter motif, and disruption of this interaction relieves repression. Structural and binding assays of the human ZnF456 domain show that ZnF6 contacts the DNA backbone and strengthens affinity. In human erythroid cells, ZnF0-dependent tetramerization supports stable protein accumulation and NuRD engagement; engineered monomers can retain DNA binding yet repress fetal globin poorly. This role is distinct from context-dependent transcriptional activation and does not assign chromatin-remodeling ATPase chemistry to BCL11A.

molecular function: DNA-binding transcription repressor activity, RNA polymerase II-specific · directly involved in: negative regulation of transcription by RNA polymerase II · locations: nucleus

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Beta Thalassemia	untyped Modifier	mechanism: Fetal Hemoglobin Modulation
Sickle Cell Disease	untyped Modifier

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
Dias-Logan syndrome MONDO:0014914	AD	Definitive 2020-09-01	no dismech entry

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.